The on-going objectives of this project are to develop predictive hypotheses about chemical-induced immunotoxicity. This can be achieved with a knowledge of the distribution and metabolism of a compound in conjunction with an understanding of the molecular biology inherent in in vitro assays of immune cell function. We are in the process of developing three immunoregulatory circuit models based on recognized (cancer chemotherapeutic agents, benzene) and postulated (estrogens) mechanisms of chemical/immunological interaction. The models include: (1) lectin-induced lymphocyte agglutination (early event) in conjunction with blastogenesis (late event); (2) lymphokine-induced macrophage agglutination (early event) in conjunction with cytostasis (late event) and analysis of lymphokine production by lectin-stimulated lymphocytes using these assays; and (3) lymphocyte and macrophage-mediated cytostasis. This approach should potentially identify chemical metabolites which have "specific" effects on various components of host defense.